Patterns of cardiovascular adaptation in hypertension have usually been explained in terms of autoregulation, vascular reactivity (including changes in vessel structure, and abnormalities in sodium and body fluid volumes. Less accepted is the possibility that neurochemical abnormalities in brain function, alone or in combination with alterations in peripheral sympathetic activity, may either account for or contribute to the evolution of renal hypertension. Because the integrative functions of the central nervous system (CNS) include regulation of the harmony of the internal environment, a detailed investigation of the role of the CNS in renal hypertension is mandated. Thus the objective of the proposed research is to uncover the mechanisms underlying a neurohormonal link between the area postrema in the brainstem and the renal pressor system. Three lines of research are proposed to characterize the physiological, neurophysiological and neurochemical bases for the role of the area postrema in renal hypertension. Initial observations that AP ablation prevents the development of one-kidney one clip hypertension will be extended to investigate the effect of AP removal on the onset of two-kidney one clip and two-kidney two clip hypertension. Detailed analysis of the effects of AP ablation upon the established phase of renal hypertension and upon hemodynamic, fluid volume and neurogenic factors in all phases of the three hypertensive models will also be undertaken. Second, the neuroanatomical and neurophysiological relationship of the area postrema to other cardiovascular brainstem regions will be characterized. Possible altered function of the area postrema neural pressor pathway and its interactions with CNS baroreceptor reflex mechanisms during the course renovascular hypertension will be evaluated. Finally, we will assess the participation of brainstem and hypothalamic adrenergic, angiotensinergic and opiate neurochemical mechanisms in two of the models of renal hypertension, with and without area postrema ablation, by means of radioligand-receptor binding studies and measurement of parameters of adrenergic neurotransmission.